对于需要量增加、吸收减少和丢失者进行叶酸补充以预防叶酸缺乏。在妊娠期和哺乳期,叶酸的每日推荐量 (RDA) 从 400 至 600 μg/日不等,取决于膳食、叶酸强化、社会经济地位和个人病史等因素。在特定患者人群中,建议较高剂量(最高为 5 mg/日)。[24]Wilson RD, Audibert F, Brock JA, et al; Genetics Committee. Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies. J Obstet Gynaecol Can. 2015;37:534-552.http://www.jogc.com/article/S1701-2163%2815%2930230-9/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26334606?tool=bestpractice.com
一项系统评价评估了孕期口服补充叶酸对母体血液学/生物学参数和妊娠结局影响,结果发现,对于早产、死胎或新生儿死亡等妊娠结局的益处没有确切证据;然而,但接受叶酸补充的孕妇巨幼红细胞性贫血的发生率明显下降。[34]Lassi ZS, Salam RA, Haider BA, et al. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev. 2013;(3):CD006896.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006896.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23543547?tool=bestpractice.com
由于补充叶酸的相关临床试验证明叶酸补充可预防大多数胎儿神经管缺陷 (NTD),因而不仅广泛实施了对谷物产品的叶酸强化,而且修改了对计划怀孕女性的叶酸补充建议。[35]MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338:131-137.http://www.ncbi.nlm.nih.gov/pubmed/1677062?tool=bestpractice.com[36]Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327:1832-1835.http://www.nejm.org/doi/full/10.1056/NEJM199212243272602#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/1307234?tool=bestpractice.com为了最大程度预防 NTD,在妊娠前 4 周结束时,计算的最佳红细胞叶酸水平是 1000 至 1300 nmol/L (442-574 ng/mL),此时神经管已经闭合。[37]Crider KS, Devine O, Hao L, et al. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014;349:g4554.http://www.bmj.com/content/349/bmj.g4554.longhttp://www.ncbi.nlm.nih.gov/pubmed/25073783?tool=bestpractice.com达到上述叶酸水平的口服摄入量显著不同,取决于:膳食、叶酸强化、社会经济地位和个人病史。
在孕前期补充叶酸预防 NTD 和相关先天性异常的指南将女性分为低风险(没有 NTD 或叶酸相关性先天性畸形的个人或家族史)、中风险(有 NTD 家族史、在患者或男性伴侣中有叶酸相关性先天性畸形的个人史或糖尿病、致畸药物用药或吸收不良患者)和高风险(患者或其男性伴侣有 NTD 个人史或患者有生育 NTD 婴儿既往史)。[24]Wilson RD, Audibert F, Brock JA, et al; Genetics Committee. Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies. J Obstet Gynaecol Can. 2015;37:534-552.http://www.jogc.com/article/S1701-2163%2815%2930230-9/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26334606?tool=bestpractice.com对欧洲指南的回顾显示,各国的建议存在差异,但对叶酸补充建议相似,都是在妊娠前 3 个月开始,剂量逐渐增加,防止复发性 NTD。[38]Cawley S, Mullaney L, McKeating A, et al. A review of European guidelines on periconceptional folic acid supplementation. Eur J Clin Nutr. 2016;70:143-154.http://www.nature.com/ejcn/journal/v70/n2/full/ejcn2015131a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/26350391?tool=bestpractice.com
对于患有慢性溶血性疾病和长期透析的患者应每日给予叶酸补充。对有吸收不良性疾病的患者针对原有病因进行治疗和/或补充叶酸能够改善血清叶酸水平。在一些国家维生素的非医学应用和叶酸强化谷物对于消除叶酸缺乏做出了很大贡献。[39]Selhub J, Rosenberg IH. Public health significance of supplementation or fortification of grain products with folic acid. Food Nutr Bull. 2008;29(2 suppl):S173-S176.http://www.ncbi.nlm.nih.gov/pubmed/18709890?tool=bestpractice.com
使用甲氨蝶呤、乙胺嘧啶和甲氧苄啶等药物的患者,需要亚叶酸(亚叶酸钙)口服或肠外使用,因为他们不能还原叶酸。